Cellular therapies, T cell therapies in particular, have shown remarkable success in treating hematological tumors and show promise in the treatment of solid tumors. These treatments require isolation of a patient's PBMC's or T cells and subsequent expansion (activation and proliferation) to generate a personalized therapeutic dose.
For the most part this type of personalized therapy consists of removing blood cells from cancer patients; isolating and activating T cells; genetically modifying the T cells thereby programming those cells to recognize and attack cancer cells; expanding the T cells; and, lastly, introducing those cells back into the body so the patient's immune system can take over. Activation is a critical component of the whole process as it is required for efficient introduction of genetic material and for robust expansion.
Several technology platforms exist in the commercial space, super paramagnetic, nonpyrogenic polystyrene beads with antibodies covalently bound to the surface, such as Dynabeads® CD3/CD28 CTS™ (Life Technologies, Beverly, Mass.) is one of the most widely used to provide for isolation, activation and expansion of T cells. Still, in using bead based clustering and cell activation, significant cell loss is observed using the bead platform. This is related to bead removal after cell expansion is complete. Alternate technologies, such as the activator from StemCell Technologies that circumvent the issue of bead removal, are not very effective for cell activation, particularly early in the activation phase when the viral transduction is generally carried out.
As such a new technology platform is desired that will provide novel approaches to cluster the T-cell surface receptors required for T cell activation and provide co-stimulatory signals to increase proliferation.